DESCRIPTION: It is indicated that the basic objectives of this application are the exploration, development and application of the tandem (4+2)/(3+2) cycloaddition reaction of the nitroalkene functional group. It is noted that the program is divided into two major sections with specific aims but unified in the common theme of new reaction chemistry for the preparation of biologically active alkaloids and carbohydrates. Both sections are divided into methodological and target synthesis subsections. The principal investigator states that the methodological goals of the first section are to expand the scope of the fused mode tandem (4+2)/(3+2)-cycloaddition in both inter- and intramolecular modes by investigation of structural modification in nitroalkene, dienophile, dipolarophile, and connecting tether. It is indicated that these basic developments are guided by the need for certain structural and stereochemical attributes in the target compounds to be synthesized. New reaction chemistry is to be developed to allow the introduction of heteroatom functions in the products. The synthesis targets addressed in the first section belong to the pyrrolizidine and indolizidine families of alkaloids. It is reported that among the more interesting compounds in the pyrrolizidine family are the necines, detoxinin and a newly isolated class of alexines. The principal investigator indicates that a new class of compounds called isoalexines is proposed for synthesis and that in the indolizidine class, two important, biologically active compounds, swainsonine and castanospermine are targeted for synthesis along with various structural analogs that are readily accessible by use of the tandem cycloaddition strategy. It is noted that the methodological goals of the second section are to expand the scope of bridged mode tandem (4+2)/(3+2)-cycloaddition and that this newest entry to the tandem family allows for rapid and selective construction of highly functionalized cyclohexanes, pyrans and cyclopentanes. The principal investigator suggests that extensive elaboration of the nitroalkene, and coupled dienophile / dipolarophile is planned that would allow for the creation of additional rings and incorporate heteroatom functionality at various positions. It is noted that the synthesis targets selected for the bridged mode tandem cycloaddition are structurally quite diverse representing such important classes of biologically active compounds as the sialic acids (N-acetylneuraminic acid) amino carbasugars, amino sugars, and other important inhibitors of glycoprotein processing such as mannosidase inhibitors, glycosidase inhibitors and trehalase inhibitors (trehazolin).